Infectious diseases remain the leading cause of death of children worldwide. New therapeutics are urgently needed, to replace current treatments that are being compromised by resistance phenomena, and to combat emerging threats. St. Jude Children's Research Hospital is the ideal pediatric research and treatment center to lead training in this effort. The hospital's translational and collaborative research environment combined with its expertise and infrastructure are well suited for therapeutic development. With the ever present threat of infection amongst our immunocompromised pediatric patient population, St. Jude has developed a mature infectious disease program that dates from its establishment over 50 years ago. This program includes research in influenza, HIV/AIDS, respiratory infections and malaria that is recognized both nationally and internationally. More recently, institutional initiatives in structural biology and chemical biolog have brought expertise in structure-based drug discovery, high throughput screening and medicinal chemistry. These are linked to an on-site GMP manufacturing facility and extensive clinical trials capability. In this application, we are requesting support for a structured and focused postdoctoral training program entitled Training in the Design and Development of Infectious Disease Therapeutics that has been designed to take advantage of this environment that is rather unique in a hospital/academic setting. The broad goals of the program are to characterize the pathogenic mechanisms of micro-organisms, to identify suitable targets for therapeutic intervention, and to develop vaccines and lead drug compounds into safe and effective medicines. We are seeking support for three postdoctoral trainees, and one additional trainee will be supported by St. Jude. The 14 preceptors in the program are faculty members from the departments of Infectious Diseases, Structural Biology, and Chemical Biology and Therapeutics. Well-funded collaborations between these preceptors provide the firm basis for the proposed training program that will feature a cross-disciplinary approach to therapeutic development. In addition, four clinical collaborators will provide training in patient care, clinical trials, and international medicine, and four training collaborators will help to provide training in essential specialized techniques. To provide a broad educational foundation for the trainees and to establish institutional identity, we have developed a comprehensive core course that will also feature instruction in key areas of personal development such as grant writing skills, ethics and mentoring. To promote eventual independence, trainees will also be required to apply for independent funding and to develop their own research projects. Each trainee will be guided by a selected `team' of mentors with the task of facilitating trainee development and independence. Finally, the training program will feature determined efforts to recruit URM trainees, and a sophisticated evaluation process to track success and identify areas for improvement.